A proprietary and confidential information about facilities and processes used in the manufacturing, processing, packaging and excipients can be included in Drug Master File (DMF) and submitted to the USFDA in support of applications and other Drug Master Files. Drug Master File submission is not mandatory; however, manufacturers would like to submit the DMF to maintain the confidentiality of proprietary information for the holder.
The information pertaining to APIs/Intermediates, Packaging Materials, Excipients and facilities can be submitted to the USFDA under Type II, Type III, Type IV and Type V DMFs respectively.
Generic Drug User Fee Act (GDUFA II) is applicable for Type II DMFs, which is intended for submission of information for active pharmaceutical ingredients. The type II DMFs would be available to access through Letter of Access (LoA) to the applicants to refer the information in their applications (ANDA/NDA/IND/DMF) only once the Initial Completeness Assessment of type II DMF is completed by the USFDA. Technical review of the DMF shall be performed by the USFDA in connection with other applications. Any queries raised by the USFDA on DMF content will delay the approval of the application referred by the applicant.
Freyr has a Regulatory team with deep understanding and experience in USDMF gap analysis, authoring and submission in eCTD format, along with managing and updating the DMFs, as per the latest guidelines by the FDA.
Regulatory submission strategy for different types of DMFs for drug substance (Type II), packaging materials (Type III) and Excipients (Type IV)
Identifying the Regulatory starting material
Guidance on selection of route of synthesis for Drug Substance in line with US FDA expectations
Support in designing the limits for impurities in starting materials, intermediates and their carry over to Active Pharmaceutical Ingredients (APIs)
Designing of specifications for starting materials, in-process, intermediates and drug substance
Support in setting the strategy and limits for genotoxic impurities and elemental impurities in intermediates or Drug Substances
Review support for finalization of development report with Quality by Design (QbD)
Guidance on designing the protocols for stability studies, process validation, hold time study and forced degradation studies for Drug Master File submission
Review of executed batch manufacturing records for the adequacy
Preparation and submission of Drug Master Files in line with GDUFA, Initial completeness assessment (ICA) requirements for Drug Substances
Guidance for GDUFA fee compliance
Publishing of DMFs in eCTD format as per current USFDA guidelines and requirements
Regulatory strategy, preparation and submission of amendments and annual reports for already registered Drug Master Files
Regulatory strategy, preparation and submission of the response to health authority queries